MSH3 c.2006G>A, p.(Arg669Gln)

Reasoning

No applicable MSH3-specific VCEP or gene framework was found, so the supplied generic PM2 supporting threshold of allele frequency <=0.0001 applies. The default all-comers gnomAD v4.1 AF is 4.46249e-05 (72/1,613,448 alleles; homozygotes=0), and gnomAD v2.1 AF is 2.38798e-05 (6/251,258 alleles; homozygotes=0); both are below 0.0001. The non-cancer subsets are concordant: gnomAD v2.1 non-cancer exomes AF=2.1122e-05 (5/236,720 alleles) and gnomAD v3.1 non-cancer genomes AF=2.70933e-05 (4/147,638 alleles), each with zero homozygotes. Therefore, PM2 is met at supporting strength.

Rule

{'source': 'generic_acmg_svi', 'threshold': 'allele frequency <=0.0001', 'strength': 'supporting', 'population_source': 'all-comers gnomAD v2.1/v4.1 by default because no governing VCEP specifies another source; non-cancer subsets are concordant'}

Evidence considered

• Default all-comers gnomAD v4.1 reports AF=4.46249e-05 from 72/1,613,448 alleles, with zero homozygotes.
• Default all-comers gnomAD v2.1 reports AF=2.38798e-05 from 6/251,258 alleles, with zero homozygotes.
• Concordant non-cancer subsets report AF=2.1122e-05 in gnomAD v2.1 non-cancer exomes and AF=2.70933e-05 in gnomAD v3.1 non-cancer genomes, with zero homozygotes in both.
• The supplied generic ClinGen SVI PM2 supporting threshold is allele frequency <=0.0001.

Sources

Reasoning

The variant is a missense substitution, NM_002439.5:c.2006G>A (p.Arg669Gln), so REVEL is the sole applicable computational path. The REVEL score is 0.202, meeting the generic ClinGen SVI BP4 supporting threshold of <=0.29. It does not meet the stronger BP4 thresholds of <=0.183 (moderate) or <=0.016 (strong). SpliceAI and BayesDel were not used because they are not the calibrated path for this missense BP4 assessment, and no MSH3-specific VCEP specification was available.

Rule

missense_only; REVEL_BP4_supporting <= 0.29; moderate <= 0.183; strong <= 0.016

Evidence considered

• The normalized consequence is missense, NM_002439.5:c.2006G>A (p.Arg669Gln), so REVEL is the applicable BP4 path and SpliceAI is not used.
• REVEL score: 0.202; generic ClinGen SVI calibration assigns BP4 supporting at <=0.29, moderate at <=0.183, and strong at <=0.016 (Pejaver et al. 2022, PMID:36413997).

Sources

Reasoning

The variant is a missense substitution, NM_002439.5:c.2006G>A (p.Arg669Gln), so REVEL is the sole applicable computational path. The REVEL score is 0.202, which does not meet the generic ClinGen SVI PP3 supporting threshold of >=0.644; the stronger PP3 thresholds are also not met. SpliceAI and BayesDel were not used because they are not the calibrated path for this missense PP3 assessment, and no MSH3-specific VCEP specification was available.

Rule

missense_only; REVEL_PP3_supporting >= 0.644; moderate >= 0.773; strong >= 0.932

Evidence considered

• The normalized consequence is missense, NM_002439.5:c.2006G>A (p.Arg669Gln), so REVEL is the applicable PP3 path and SpliceAI is not used.
• REVEL score: 0.202; generic ClinGen SVI calibration assigns PP3 supporting at >=0.644, moderate at >=0.773, and strong at >=0.932 (Pejaver et al. 2022, PMID:36413997).

Sources

Reasoning

PP5 is restricted here to an exact-variant ClinVar expert-panel classification of Pathogenic or Likely pathogenic. The exact variant NM_002439.5:c.2006G>A (p.Arg669Gln) has no ClinVar expert-panel submission; the audit reports zero expert-panel submissions, with available assertions limited to single-submitter laboratory classifications of uncertain significance or likely benign. Therefore PP5 is not met. No publication can substitute for the required expert-panel classification.

Rule

PP5 supporting only when an exact-variant ClinVar expert panel classifies the variant as Pathogenic or Likely pathogenic; expert-panel evidence is absent.

Evidence considered

• The exact-match ClinVar audit reports 0 expert-panel submissions and only single-submitter laboratory assertions, including uncertain significance and likely benign classifications.
• Under the specified rule, ordinary laboratory submissions, aggregate labels, and non-expert assertions cannot trigger PP5.

Sources

Reasoning

No applicable MSH3-specific VCEP or gene framework was found, so the supplied generic ACMG/AMP BA1 threshold of allele frequency >=0.05 applies. The highest observed allele frequency is 4.46249e-05 in all-comers gnomAD v4.1 (72/1,613,448 alleles; homozygotes=0), far below 0.05; the gnomAD v2.1 all-comers frequency is 2.38798e-05 (6/251,258 alleles). Therefore, BA1 is not met.

Rule

{'source': 'generic_acmg_amp', 'threshold': 'allele frequency >=0.05', 'population_source': 'all-comers gnomAD v2.1/v4.1 by default because no governing VCEP specifies another source'}

Evidence considered

• All-comers gnomAD v4.1 reports 72/1,613,448 alleles, AF=4.46249e-05, with zero homozygotes.
• All-comers gnomAD v2.1 reports 6/251,258 alleles, AF=2.38798e-05, with zero homozygotes.
• The supplied generic ACMG/AMP BA1 stand-alone threshold is allele frequency >=0.05.

Sources

Reasoning

No applicable MSH3-specific VCEP or gene framework was found, so the supplied generic BS1 threshold of allele frequency >=0.01 applies. The highest observed allele frequency is 4.46249e-05 in all-comers gnomAD v4.1, with the highest reported subpopulation frequency 6.66889e-05 in Admixed American individuals; both are below 0.01. The gnomAD v2.1 all-comers AF is 2.38798e-05. Therefore, BS1 is not met.

Rule

{'source': 'generic_acmg_svi_default', 'threshold': 'allele frequency >=0.01', 'population_source': 'all-comers gnomAD v2.1/v4.1 by default because no governing VCEP specifies another source'}

Evidence considered

• All-comers gnomAD v4.1 reports overall AF=4.46249e-05 and highest observed subpopulation AF=6.66889e-05 in Admixed American individuals.
• All-comers gnomAD v2.1 reports overall AF=2.38798e-05 and highest observed subpopulation AF=8.67303e-05 in Admixed American individuals.
• The supplied generic BS1 threshold is allele frequency >=0.01.

Sources

Reasoning

BP6 is restricted here to an exact-variant ClinVar expert-panel classification of Benign or Likely benign. The exact variant NM_002439.5:c.2006G>A (p.Arg669Gln) has no ClinVar expert-panel submission; the audit reports zero expert-panel submissions. Although two laboratory submissions report Likely benign, they are ordinary single-submitter assertions and are explicitly excluded from BP6 under the governing instruction. Therefore BP6 is not met.

Rule

BP6 supporting only when an exact-variant ClinVar expert panel classifies the variant as Benign or Likely benign; expert-panel evidence is absent.

Evidence considered

• The exact-match ClinVar audit reports 0 expert-panel submissions; the available Likely benign classifications are single-submitter laboratory assertions.
• Under the specified rule, ordinary laboratory submissions, aggregate labels, and non-expert assertions cannot trigger BP6.

Sources

Reasoning

The variant is MSH3 NM_002439.5:c.2006G>A, p.Arg669Gln. No validated report of the same amino-acid change caused by a different nucleotide substitution was identified in the available case evidence. The case contains no variant-specific functional or clinical source establishing that an alternate codon change producing p.Arg669Gln is pathogenic.

Rule

PS1 requires a well-established pathogenic alternate nucleotide change producing the same amino-acid change.

Evidence considered

• The normalized variant is NM_002439.5:c.2006G>A, NP_002430.3:p.(Arg669Gln).
• The available ClinVar record reports this exact variant but does not establish a pathogenic alternate-codon substitution producing p.Arg669Gln.
• The reviewed paper extracts contain no MSH3 p.Arg669Gln or same-amino-acid comparator observation.

Still missing

• A validated same-amino-acid change at p.Arg669 from a different nucleotide substitution is needed for PS1.

Reasoning

PS2 cannot be assessed. The available case evidence does not document a proband with a confirmed de novo NM_002439.5:c.2006G>A (p.Arg669Gln) variant, nor does it provide confirmed parental genotypes demonstrating that the variant is absent in both biological parents. No maternity/paternity information, parental testing results, or validated de novo observation is available. Generic ACMG/AMP PS2 requires reliable parental testing and cannot be inferred from the variant's rarity, ClinVar record, or general disease literature.

Rule

Generic ACMG/AMP PS2: apply only when a confirmed affected proband has a confirmed de novo variant with reliable parental relationship and parental testing evidence; strength escalation requires specification-supported criteria or multiple independent observations.

Evidence considered

• No proband-level de novo finding or parental genotype data are documented in the available case evidence.
• The variant is an MSH3 missense change, NM_002439.5:c.2006G>A (p.Arg669Gln), but variant identity alone does not establish de novo occurrence.
• Generic ACMG/AMP de novo evidence requires documented parental testing; no such result is available here.

Still missing

• Documented proband phenotype and molecular test report
• Genotypes of both biological parents at NM_002439.5:c.2006G>A
• Confirmation of biological relationships and reliable de novo status

Sources

Reasoning

No applicable MSH3-specific VCEP specification was available, so generic ACMG/AMP criteria were used. The variant is a missense change, but the reviewed evidence contains no validated variant-specific functional assay, quantitative biological readout, assay controls, or reproducible experimental result demonstrating a damaging effect. The available ClinVar submission text explicitly states that the benign computational prediction had not been confirmed by functional studies; this is an absence of evidence, not positive functional evidence. PS3 therefore cannot be assessed at any strength.

Evidence considered

• The case evidence identifies NM_002439.5:c.2006G>A as the missense variant NP_002430.3:p.Arg669Gln in MSH3.
• The reviewed ClinVar submission text states that the benign REVEL prediction had not been confirmed by functional studies; it reports no completed variant-specific assay result.
• The generic ACMG/AMP guidance describes functional studies as evidence but does not report a functional assay for this variant or MSH3 p.Arg669Gln specifically.

Still missing

• A validated variant-specific functional assay with appropriate positive and negative controls and a disease-relevant readout is needed.
• No published functional study directly evaluating MSH3 p.Arg669Gln was identified among the reviewed sources.

Sources

Reasoning

No applicable MSH3-specific VCEP framework is available, so the generic ACMG/AMP PS4 concept applies: PS4 requires a statistically significant excess of the exact variant or a well-defined variant class in affected individuals compared with controls. The available evidence contains no case-control counts, odds ratio, enrichment statistic, or variant-specific affected-patient cohort for NM_002439.5:c.2006G>A (p.Arg669Gln). The cited publications were checked in the pre-computed extracts and do not mention this variant; therefore PS4 cannot be assessed rather than inferred from general MSH3 or mismatch-repair disease information.

Rule

Generic ACMG/AMP PS4: statistically significant increased prevalence of the variant or a well-defined variant class in affected individuals compared with controls; no applicable MSH3-specific VCEP rule was found.

Evidence considered

• ClinVar exact-match records show only uncertain-significance and single-submitter likely-benign laboratory assertions, not a variant-specific case-control study.
• The extracted publications do not mention MSH3 c.2006G>A/p.Arg669Gln and provide no variant-specific affected-case cohort or enrichment statistic.

Still missing

• Variant-specific affected-case count and an appropriate control comparison are unavailable.
• No odds ratio, relative risk, statistical significance, or validated enrichment threshold is available.

Sources

Reasoning

No governing MSH3 VCEP or gene-specific specification is available, and vcep_materials.json has no MSH3 domain_tables entry. The case evidence also provides no validated critical functional domain, hotspot, or residue-level functional-region annotation for MSH3 p.Arg669. Therefore PM1 cannot be established from the generic framework.

Rule

PM1 requires a variant located in a mutational hot spot or well-established critical functional domain without benign variation; a gene-specific specification takes precedence when available.

Evidence considered

• No applicable MSH3-specific VCEP framework was found, and vcep_materials.json contains an empty domain_tables object.
• The Cancer Hotspots result reports no statistically significant hotspot at MSH3 R669.
• No other validated domain or critical functional-region annotation for residue 669 is present in the case evidence.

Still missing

• A governing MSH3 domain specification or validated evidence that p.Arg669 lies in a critical functional domain or hotspot is needed.

Reasoning

No applicable MSH3-specific VCEP framework was available, so the generic ACMG/AMP PM3 definition was used. The available case evidence identifies NM_002439.5:c.2006G>A (p.Arg669Gln) as a missense variant but provides no affected-proband observation with a second pathogenic or likely pathogenic MSH3 variant, no confirmed biallelic genotype, and no phase or inheritance information establishing the variant in trans. Therefore PM3 cannot be applied.

Rule

{'framework': 'generic ACMG/AMP', 'criterion': 'PM3', 'requirement': 'Pathogenic or likely pathogenic variant established in trans with the variant under assessment in an affected individual, with strength determined by the applicable allelic evidence.', 'application': 'Not assessable without affected-proband and phase evidence.'}

Evidence considered

• No applicable MSH3-specific VCEP specification was retrieved; generic ACMG/AMP fallback was therefore required.
• The case record identifies the variant as NM_002439.5:c.2006G>A (NP_002430.3:p.Arg669Gln), but the consolidated evidence contains no affected-proband genotype, second pathogenic MSH3 variant, phase result, or inheritance information needed for PM3.
• ClinVar records conflicting submissions for the variant but does not provide documented in-trans pathogenic-variant observations or phase evidence for this assessment; classification labels were not used as evidence.

Still missing

• Affected-proband observations involving this variant are not documented.
• A second pathogenic or likely pathogenic MSH3 variant and its phase relative to c.2006G>A are not documented.
• Inheritance and parental phase information are not available.

Sources

Reasoning

The variant is missense at MSH3 residue Arg669, so PM5 is applicable in principle. However, no validated pathogenic or likely pathogenic missense comparator at the same residue was identified, and the available PM5 candidate artifact contains zero same-residue candidates and explicitly does not establish PM5 semantics.

Rule

PM5 requires a novel missense change at a residue where a different missense change is established as pathogenic or likely pathogenic.

Evidence considered

• The normalized protein change is NP_002430.3:p.(Arg669Gln).
• The available same-residue comparator search contains zero candidates and does not establish a PM5-qualifying comparator.
• No reviewed paper extract reports a pathogenic alternate missense substitution at residue 669.

Still missing

• A validated pathogenic or likely pathogenic missense substitution at MSH3 residue Arg669 is needed for PM5.

Reasoning

PM6 cannot be assessed. The available evidence does not report NM_002439.5:c.2006G>A (p.Arg669Gln) as presumed de novo in an affected proband and provides no supporting parental testing, family structure, maternity/paternity assessment, or independent clinical report. A general ClinVar submission statement that the variant has not been reported in MSH3-associated familial adenomatous polyposis is not evidence of presumed de novo occurrence. PM6 cannot be inferred from population frequency, phenotype context, or a database classification.

Rule

Generic ACMG/AMP PM6: apply only for a presumed de novo variant in an affected individual when parental testing is unavailable but the clinical and family evidence supports that interpretation; do not substitute rarity or database absence for de novo evidence.

Evidence considered

• No case report or clinical record in the available evidence describes this MSH3 variant as presumed de novo.
• No parental testing, family structure, or maternity/paternity information is available to support a presumed de novo interpretation.
• Absence of a prior report in a ClinVar submission is not evidence that the variant arose de novo.

Still missing

• A published or clinical report describing the affected proband
• Evidence that the variant was presumed de novo despite unavailable parental testing
• Phenotype, family structure, maternity/paternity, and independent confirmation details

Sources

Reasoning

PP1 cannot be assessed. No affected relatives carrying NM_002439.5:c.2006G>A (p.Arg669Gln), unaffected relatives lacking the variant, informative meioses, family segregation table, or phenotype concordance data are provided. The literature extracts available for this case do not report this MSH3 variant or any variant-specific segregation observation. A ClinVar classification or general MSH3 disease discussion cannot be used as a substitute for observed cosegregation in informative family members.

Rule

Generic ACMG/AMP PP1: apply only when a variant cosegregates with disease in informative affected and/or unaffected relatives; strength depends on the number and informativeness of independent meioses under an applicable calibrated framework.

Evidence considered

• No affected-relative or unaffected-relative segregation data are documented for this variant.
• No informative meioses or independent family observations are available.
• The extracted literature does not report MSH3 c.2006G>A/p.Arg669Gln or variant-specific segregation findings.

Still missing

• Genotypes and phenotypes of informative relatives
• Number of informative meioses and independent families
• Variant-specific segregation table or clinical reports

Sources

Reasoning

The variant is missense, and the case contains general support for MSH3 loss of function as a disease mechanism. However, no applicable MSH3-specific framework or quantitative evidence demonstrates both that pathogenic missense variants are a common mechanism and that benign missense variation is uncommon, as required for PP2.

Rule

PP2 requires a missense variant in a gene for which missense variation is a common disease mechanism and benign missense variation is uncommon.

Evidence considered

• The variant consequence is missense: NP_002430.3:p.(Arg669Gln).
• The case-level gene context supports MSH3 loss of function as a germline disease mechanism, but does not quantify benign versus pathogenic missense variation.
• No MSH3-specific VCEP specification defining PP2 eligibility was available.

Still missing

• Gene-specific evidence showing a low rate of benign missense variation and a meaningful contribution of pathogenic missense variants is needed.

Reasoning

No applicable MSH3-specific VCEP framework is available, so the generic ACMG/AMP PP4 concept applies: the patient's phenotype or family history must be highly specific for a disease with a single-gene etiology. The case evidence does not provide a patient phenotype, family history, or a disease-specific clinical presentation linked to this exact variant. General descriptions of mismatch-repair or endometrial-cancer phenotypes cannot establish PP4 for this variant or for MSH3 without patient-specific, highly specific phenotype data.

Rule

Generic ACMG/AMP PP4: patient's phenotype or family history is highly specific for a disease with a single-gene etiology; insufficient patient-specific phenotype data are available.

Evidence considered

• The available ClinVar record contains no patient phenotype or family-history details for the exact variant.
• The extracted literature discusses mismatch-repair and endometrial-cancer phenotypes generally but does not provide patient-specific or MSH3 c.2006G>A-specific phenotype evidence.

Still missing

• Patient-level phenotype and family-history information is unavailable.
• No validated MSH3-specific phenotype-to-disease specificity rule is available.

Sources

Reasoning

BS2 requires the variant to be observed in healthy individuals in a manner inconsistent with the disease model, typically including homozygous or hemizygous observations for a fully penetrant dominant disorder or affected-state observations for a recessive disorder. gnomAD reports zero homozygotes for this variant in the available all-comers and non-cancer datasets, and its heterozygote observations do not establish that carriers are clinically unaffected because individual phenotype and ascertainment data are unavailable. No independent healthy-carrier or disease-model evidence sufficient for BS2 was provided, so BS2 cannot be assessed.

Rule

{'source': 'generic_acmg_amp', 'requirement': 'observation in healthy individuals in a manner inconsistent with the disease model', 'population_source': 'population frequency data alone are insufficient without phenotype-linked evidence'}

Evidence considered

• All-comers gnomAD v4.1 reports zero homozygotes; the non-cancer genome subset also reports zero homozygotes.
• All-comers gnomAD v2.1 reports zero homozygotes; the non-cancer exome subset also reports zero homozygotes.
• The available population records do not provide individual clinical phenotype or penetrance information for the observed heterozygotes.

Still missing

• No phenotype-linked healthy-carrier or disease-model evidence establishing that this variant occurs in unaffected individuals in a BS2-compatible pattern.

Sources

Reasoning

No applicable MSH3-specific VCEP specification was available, so generic ACMG/AMP criteria were used. The reviewed evidence contains no validated variant-specific functional assay showing that MSH3 p.Arg669Gln has a normal effect, and there are no quantitative benign functional results, assay controls, or disease-relevant biological measurements from which BS3 strength could be calibrated. Computational prediction, population frequency, and clinical classifications cannot substitute for the functional evidence required for BS3. BS3 therefore cannot be assessed at any strength.

Evidence considered

• The case evidence identifies NM_002439.5:c.2006G>A as the missense variant NP_002430.3:p.Arg669Gln in MSH3.
• The reviewed ClinVar submission text does not provide a normal-function assay result and instead notes that functional confirmation was unavailable.
• The generic ACMG/AMP guidance provides general functional-study criteria but contains no variant-specific benign assay result for MSH3 p.Arg669Gln.

Still missing

• A validated variant-specific functional assay with appropriate controls and a disease-relevant normal-function readout is needed.
• No published functional study directly evaluating MSH3 p.Arg669Gln was identified among the reviewed sources.

Sources

Reasoning

BS4 cannot be assessed. The available case evidence does not identify affected relatives who were tested and found not to carry NM_002439.5:c.2006G>A (p.Arg669Gln), and it does not provide family phenotyping, age-related penetrance information, or informative non-segregation observations. The absence of reported family data is not equivalent to demonstrated non-segregation, and the variant's population frequency or conflicting ClinVar classifications do not satisfy BS4.

Rule

Generic ACMG/AMP BS4: apply only when an affected individual or affected relatives expected to carry the disease-associated variant test negative, with phenotype and family structure sufficiently informative to interpret the non-segregation.

Evidence considered

• No affected relative with a reliable negative genotype is reported.
• No informative family-level non-segregation result or phenotype/penetrance assessment is available.
• Population observations and ClinVar classifications do not establish non-segregation in a family.

Still missing

• Affected relatives tested for the variant
• Reliable negative genotypes in affected relatives
• Phenotype definitions, ages, penetrance, and family structure sufficient to interpret non-segregation

Sources

Reasoning

The variant is missense and the case contains general support for MSH3 loss of function as a disease mechanism, but that information alone does not establish that MSH3 disease is primarily caused by truncating variants or that missense variants are rarely pathogenic. No gene-specific quantitative missense-mechanism evidence or specification supports BP1.

Rule

BP1 requires a missense variant in a gene for which primarily truncating variants are known to cause disease and pathogenic missense variation is uncommon.

Evidence considered

• The variant consequence is missense: NP_002430.3:p.(Arg669Gln).
• The case-level gene context supports MSH3 loss of function as a germline disease mechanism, but does not establish the predominance or rarity requirements for BP1.
• No MSH3-specific VCEP specification defining BP1 eligibility was available.

Still missing

• Gene-specific evidence that MSH3 disease is predominantly caused by truncating variants with rare pathogenic missense variation is needed.

Reasoning

No applicable MSH3-specific VCEP framework was available, so the generic ACMG/AMP BP2 definition was used. The available case evidence provides no unaffected individual or affected individual with a second pathogenic or likely pathogenic variant in cis with NM_002439.5:c.2006G>A (p.Arg669Gln), and no phase or co-occurrence data are documented. Therefore BP2 cannot be applied.

Rule

{'framework': 'generic ACMG/AMP', 'criterion': 'BP2', 'requirement': 'Variant observed in trans with a pathogenic or likely pathogenic variant, or in cis with a pathogenic variant, in an unaffected individual or affected individual, as applicable to the generic criterion definition.', 'application': 'Not assessable without individual-level co-occurrence and phase evidence.'}

Evidence considered

• No applicable MSH3-specific VCEP specification was retrieved; generic ACMG/AMP fallback was therefore required.
• The consolidated case evidence contains no unaffected- or affected-individual co-occurrence data, second pathogenic MSH3 variant, confirmed cis phase, or inheritance information needed for BP2.
• ClinVar records conflicting submissions for the variant but does not provide documented cis co-occurrence or phase evidence for this assessment; classification labels were not used as evidence.

Still missing

• No individual-level co-occurrence observation is documented.
• A second pathogenic or likely pathogenic MSH3 variant in cis with c.2006G>A is not documented.
• Phase information confirming cis configuration is not available.

Sources

Reasoning

No applicable MSH3-specific VCEP framework is available, and the available evidence does not document a confirmed alternate molecular or clinical explanation that accounts for the relevant phenotype while excluding this variant's causal role. General gene-level cancer information, a single somatic COSMIC observation, and non-expert ClinVar laboratory classifications do not establish BP5. No BP5-specific numeric rule or likelihood-ratio threshold is available in the governing evidence, so no numeric comparison can be performed.

Rule

Generic ACMG/AMP BP5 concept: an alternate molecular basis for the patient's phenotype is identified; no qualifying alternate explanation or applicable numeric threshold is available.

Evidence considered

• ClinVar provides only non-expert single-submitter classifications and does not establish an alternate cause for a defined phenotype.
• OncoKB reports no variant-specific reviewed evidence; its gene-level cancer context cannot establish BP5.

Still missing

• A confirmed alternate molecular or clinical cause for the relevant phenotype is unavailable.
• No applicable MSH3-specific BP5 rule or threshold is available.

Sources