About MYH7
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MYH7 c.4909G>A, p.(Ala1637Thr)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen MYH7 VCEP v2.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BS1Strong
BS1 · strong
gnomAD grpmax FAF (v2.1: 0.00062247; v4.1: 0.00080614) exceeds the VCEP BS1 threshold of ≥0.0001 for MYH7. The variant is present at highest frequency in the African/African American population (v2.1: 22/24,960 alleles, 0.088%; v4.1: 74/74,932 alleles, 0.099%) with one homozygote in each dataset. Per VCEP specifications, BS1 may be used as standalone evidence to classify a variant as Likely Benign in the absence of conflicting data.
BP6Supporting
BP6 · supporting
Expert panel ClinGen Cardiomyopathy Variant Curation Expert Panel classified as Likely benign.
Recorded classification: Likely benign
ClinGen Cardiomyopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MYH7 Version 2.0 v2.0 criteria-combination framework: matched Rule18 (1 Benign.Strong + 1 Benign.Supporting) with applied criteria: BS1 strong benign, BP6 supporting benign; maps to Likely Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
128 / 1,614,080 alleles
gnomAD v4.1: 128 / 1,614,080 alleles. Recorded AF 7.93021e-05. Recorded homozygote count 1.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 8.83986e-05; MAF= 0.00884%, 25/282810 alleles, homozygotes = 1) and has highest observed frequency in the African/African American population (AF= 0.00088141; MAF= 0.08814%, 22/24960 alleles, homozygotes = 1); grpmax FAF= 0.00062247.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016291951775822744, 3/18414 alleles, homozygotes = 0).
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
12 reported laboratory submissions
7 Likely benign · 3 Uncertain significance · 1 Benign · 1 Uncertain Significance. ClinVar API review status: reviewed by expert panel.
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen MYH7 VCEP v2.0, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 15 not met · 0 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000257.4:c.4909G>A (p.Ala1637Thr) in MYH7 meets BS1 at strong_benign strength: gnomAD grpmax FAF (v2.1: 0.00062247; v4.1: 0.00080614) exceeds the VCEP threshold of ≥0.0001 for MYH7, with highest frequency in the African/African American population (v4.1: 0.099%) and one homozygote observed in each gnomAD dataset.
No pathogenic criteria are met. PM1 is not applicable (codon 1637 is outside the VCEP-defined cluster region of codons 167-931). PM2 is not met (gnomAD frequency far exceeds the ≤0.00004 threshold). PP3 is not met (REVEL 0.577 < 0.70 threshold). PS3/PS4/PM5/PM6/PP1/PS1/PS2 all lack supporting evidence.
Per VCEP BS1 specifications, 'Criterion BS1 may only be used as standalone evidence to classify a variant as Likely Benign in the absence of conflicting data.' No conflicting pathogenic evidence exists. All pathogenic criteria are either not met or not applicable. This variant is classified as Likely Benign.
This assessment is concordant with the ClinGen Cardiomyopathy Expert Panel classification of Likely Benign (ClinVar VariationID: 43044, review status: reviewed by expert panel), with 7 of 12 clinical laboratories also reporting Likely Benign or Benign.
One HCM case harboring this variant was reported by Nuñez et al. 2013 (PMID:23782526), in which all five in silico tools predicted A1637T as neutral. The variant was observed alongside established pathogenic mutations in the same cohort but was not functionally characterized.
No criteria match.
Met · 2
BS1 StronggnomAD grpmax FAF (v2.1: 0.00062247; v4.1: 0.00080614) exceeds the VCEP BS1 threshold of ≥0.0001 for MYH7. The variant is present at highest frequency in the African/African American population (v2.1: 22/24,960 alleles, 0.088%; v4.1: 74/74,932 alleles, 0.099%) with one homozygote in each dataset. Per VCEP specifications, BS1 may be used as standalone evidence to classify a variant as Likely Benign in the absence of conflicting data. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF=0.00062247 (≥0.0001 BS1 threshold)
- gnomAD v4.1 grpmax FAF=0.00080614 (≥0.0001 BS1 threshold)
- African/Af Am: v2.1 22/24
- 960 (0.088%)
- v4.1 74/74
- 932 (0.099%)
- 1 homozygote in each gnomAD dataset
Sources
Not met · 15 · evaluated, threshold not reached
PS1 No other nucleotide change is known to produce the same amino acid change p.(Ala1637Thr) that has been classified as pathogenic. PS1 requires an established pathogenic variant at the same amino acid position. Details ▾Hide ▴
Evidence considered
- No pathogenic variant with the same amino acid change identified
PS2 No de novo occurrence of NM_000257.4:c.4909G>A has been reported in any reviewed publication or database. The VCEP requires confirmation of both maternity and paternity for PS2 application. Details ▾Hide ▴
Evidence considered
- No de novo data found in reviewed sources
Still missing
- No de novo testing data available
PS3 No functional studies have been performed on p.(Ala1637Thr). Nuñez et al. 2013 (PMID:23782526) identified this variant in 1 of 104 HCM patients and all five in silico tools (SIFT, Pmut, PolyPhen, SNAP, PhDSNP) predicted the variant as neutral, but in silico predictions do not constitute functional evidence per VCEP PS3 specifications. No in vitro splicing assay, in vivo knock-in model, or biochemical assay data exist for this variant. Details ▾Hide ▴
Evidence considered
- In silico prediction of neutrality by all 5 tools in Nuñez et al. 2013
- not PS3 functional evidence
- No variant-specific functional assays exist
Still missing
- No functional studies exist for this variant
Sources
PS4 No case-control study demonstrates enrichment of this variant in affected individuals compared to controls. One HCM case was observed in Nuñez et al. 2013 (1/104 probands), but the variant is present in gnomAD at a frequency inconsistent with a rare dominant disorder (v2.1: 25/282,810 alleles, v4.1: 128/1,614,080 alleles), including one homozygote in each dataset. Formal case-control analysis has not been performed. Details ▾Hide ▴
Evidence considered
- 1 HCM case in Nuñez et al. 2013 (1/104)
- gnomAD v2.1: 25/282
- 810 alleles (0.0089%)
- gnomAD v4.1: 128/1
- 614
- 080 alleles (0.0079%)
- 1 homozygote in each gnomAD dataset
Still missing
- No formal case-control analysis available
Sources
PM1 The VCEP defines the PM1 cluster region as codons 167-931 (ENST00000355349 / NM_000257.4). This variant is at codon 1637, which lies outside this region in the light meromyosin (LMN) domain. No pathogenic variant enrichment has been demonstrated for codon 1637. Details ▾Hide ▴
Evidence considered
- VCEP PM1 region: codons 167-931
- Variant at codon 1637 is outside the defined cluster region
Sources
PM2 gnomAD grpmax FAF (v2.1: 0.00062247; v4.1: 0.00080614) substantially exceeds the VCEP PM2 threshold of ≤0.00004 (upper bound 95% CI). The variant is present at highest frequency in the African/African American population (v2.1 AF=0.088%, 22/24,960 alleles; v4.1 AF=0.099%, 74/74,932 alleles) with one homozygote observed in each dataset. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF=0.00062247 >> 0.00004 threshold
- gnomAD v4.1 grpmax FAF=0.00080614 >> 0.00004 threshold
- African/Af Am: v2.1 22/24
- 960 (0.088%)
- v4.1 74/74
- 932 (0.099%)
- 1 homozygote in each dataset
Sources
PM5 No different missense variant at codon 1637 has been classified as pathogenic or likely pathogenic per VCEP-modified guidelines. The pm5_candidates search returned no comparator variants at this residue. Details ▾Hide ▴
Evidence considered
- No pathogenic/likely pathogenic missense variant identified at codon 1637
PM6 No assumed de novo occurrence of this variant has been reported without confirmation of maternity and paternity. The VCEP requires phenotype consistent with the gene but SVI guidance on the number of cases needed. Details ▾Hide ▴
Evidence considered
- No de novo data found in any reviewed source
Still missing
- No de novo reports exist
PP1 No segregation data are available for this variant. The VCEP requires ≥3 segregations (LOD score ≥0.9) for supporting, ≥5 for moderate, and ≥7 for strong evidence. Details ▾Hide ▴
Evidence considered
- No segregation data available
Still missing
- No familial segregation data exist
PP3 REVEL score is 0.577, which is below the VCEP-recommended threshold of ≥0.70 for PP3. SpliceAI delta score is 0.00, indicating no predicted splice impact. BayesDel score is −0.0637 (benign range). In silico meta-predictors do not support a pathogenic interpretation. Details ▾Hide ▴
Evidence considered
- REVEL=0.577 (<0.70 PP3 threshold)
- SpliceAI max delta=0.00 (no splice impact)
- BayesDel=−0.0637 (benign direction)
Sources
BA1 gnomAD grpmax FAF (v2.1: 0.00062247; v4.1: 0.00080614) is below the VCEP BA1 threshold of ≥0.001. The variant does not exceed the stand-alone benign allele frequency cutoff. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF=0.00062247 (<0.001 BA1 threshold)
- gnomAD v4.1 grpmax FAF=0.00080614 (<0.001 BA1 threshold)
Sources
BS3 No functional studies demonstrating no damaging effect exist for p.(Ala1637Thr). While Nuñez et al. 2013 predicted the variant as neutral by all five in silico tools, in silico predictions do not constitute functional evidence per VCEP BS3 specifications (which mirror PS3 specifications). Details ▾Hide ▴
Evidence considered
- In silico neutrality prediction from Nuñez et al. 2013
- not functional evidence
- No variant-specific functional studies exist
Still missing
- No functional studies demonstrating no damaging effect
Sources
BS4 No non-segregation data are available for this variant. The VCEP requires ≥2 non-segregations that are highly unlikely to be phenocopies or due to alternate variants. Details ▾Hide ▴
Evidence considered
- No non-segregation data available
Still missing
- No segregation or non-segregation data exist
BP2 No data are available on co-occurrence of this variant in trans or cis with a pathogenic variant. BP2 requires observation in trans with a pathogenic variant in ≥2 cases without more severe phenotype, or in cis with a pathogenic variant. Details ▾Hide ▴
Evidence considered
- No co-occurrence data available
Still missing
- No data on co-occurrence with pathogenic variants
BP4 REVEL score is 0.577, which exceeds the VCEP BP4 threshold of ≤0.40. BayesDel score is −0.0637, indicating a slight benign prediction, but the VCEP-recommended REVEL meta-predictor does not support a benign interpretation. SpliceAI delta score is 0.00, consistent with no splice impact. Details ▾Hide ▴
Evidence considered
- REVEL=0.577 (>0.40 BP4 threshold)
- SpliceAI max delta=0.00 (no splice impact)
- BayesDel=−0.0637 (benign but not the recommended meta-predictor)
Sources
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 VCEPPVS1 is not applicable for MYH7 per the ClinGen Cardiomyopathy VCEP v2.0 specifications. MYH7 missense variants are the predominant disease mechanism; null variants are also reported. This variant is a missense substitution (c.4909G>A, p.Ala1637Thr) and does not fall into PVS1 null-variant buckets. Details ▾Hide ▴
Evidence considered
- VCEP specifies PVS1 not applicable for MYH7
- Variant is missense
- not a null variant
Sources
PP2 VCEPThe ClinGen Cardiomyopathy VCEP specifies PP2 is not applicable. Regional enrichment data for MYH7 missense variants is captured by PM1 specifications (Walsh et al. 2019, PMID:30696458). Details ▾Hide ▴
PP4 VCEPThe ClinGen Cardiomyopathy VCEP specifies PP4 as not applicable due to high locus heterogeneity and non-genetic etiologies in inherited cardiomyopathies. Details ▾Hide ▴
PP5 VCEPThe ClinGen Cardiomyopathy VCEP explicitly designates PP5 as 'Not Applicable for this VCEP' per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. This criterion is not for use in the MYH7 cardiomyopathy framework. Details ▾Hide ▴
BS2 VCEPThe ClinGen Cardiomyopathy VCEP specifies BS2 as not applicable because inherited cardiomyopathies generally display reduced penetrance, variable expressivity, and adult-onset. Observation in a healthy adult does not rule out pathogenicity. Details ▾Hide ▴
BP1 VCEPThe ClinGen Cardiomyopathy VCEP specifies BP1 as not applicable because pathogenic missense variants have been reported in MYH7 alongside null variants. A missense variant in a gene where missense variants are a known disease mechanism does not qualify for BP1. Details ▾Hide ▴
BP5 VCEPThe ClinGen Cardiomyopathy VCEP specifies BP5 as not applicable. Co-occurrence with an established pathogenic or likely pathogenic variant for a non-cardiomyopathy related disease does not reduce the likelihood that a variant is independently disease-causing for cardiomyopathy. Details ▾Hide ▴
BP7 N/ABP7 applies to synonymous variants and intronic variants outside the splice consensus sequence. This variant is a missense substitution (c.4909G>A, p.Ala1637Thr) and does not qualify for BP7. SpliceAI predicts no splice impact (delta=0.00), but BP7 is structurally not applicable to missense variants. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous or intronic
- SpliceAI delta=0.00 but BP7 not applicable to missense
Sources
PS5 N/ANo reputable source has reported this variant as pathogenic. ClinVar classification is Likely Benign, reviewed by the ClinGen Cardiomyopathy Expert Panel. PS5 requires a reputable source to have recently reported the variant as pathogenic without available evidence for independent evaluation. Details ▾Hide ▴
Evidence considered
- ClinVar: Likely Benign
- expert panel reviewed
- not reported as pathogenic by any source
Sources
Identifiers
- Gene
- MYH7
- Transcript
- NM_000257.4
- Coding (HGVS c.)
- NM_000257.4:c.4909G>A
- Protein (HGVS p.)
- NP_000248.2:p.(Ala1637Thr)
- GRCh38
- chr14:23416048 C>T
- GRCh37
- chr14:23885257 C>T
- ClinVar
- 43044
Gene diagram
Every interpreted variant in MYH7, mapped onto the exon structure of NM_000257.4. Select a row to find it on the plot.
MYH7NM_000257.4
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in MYH7
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
128 / 1,614,080 alleles
AF 7.93e-05 · 1 homozygotes · FAF 0.000806
gnomAD v2.1
25 / 282,810 alleles
AF 8.84e-05 · 1 homozygotes · FAF 0.000622
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 7.9e-05 · 128 / 1,614,080 alleles · 1 hom · FAF 0.00081
| African/African American74 / 74,932 | 0.000991 hom |
| Middle Eastern2 / 6,068 | 0.00033 |
| South Asian15 / 91,088 | 0.00016 |
| Remaining individuals5 / 62,482 | 8e-05 |
| Admixed American4 / 60,008 | 6.7e-05 |
| East Asian2 / 44,898 | 4.5e-05 |
| Ashkenazi Jewish1 / 29,606 | 3.4e-05 |
| European (non-Finnish)25 / 1,180,050 | 2.1e-05 |
0 alternate alleles recorded in 2 other groups: European (Finnish), Amish.
gnomAD v2.1
AF 8.8e-05 · 25 / 282,810 alleles · 1 hom · FAF 0.00062
| African/African American22 / 24,960 | 0.000881 hom |
| East Asian1 / 19,950 | 5e-05 |
| South Asian1 / 30,616 | 3.3e-05 |
| Admixed American1 / 35,440 | 2.8e-05 |
0 alternate alleles recorded in 4 other groups: Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 7.93021e-05; MAF= 0.00793%, 128/1614080 alleles, homozygotes = 1) and has highest observed frequency in the African/African American population (AF= 0.000987562; MAF= 0.09876%, 74/74932 alleles, homozygotes = 1); grpmax FAF= 0.00080614.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 8.83986e-05; MAF= 0.00884%, 25/282810 alleles, homozygotes = 1) and has highest observed frequency in the African/African American population (AF= 0.00088141; MAF= 0.08814%, 22/24960 alleles, homozygotes = 1); grpmax FAF= 0.00062247.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016291951775822744, 3/18414 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.577
- BayesDel
- -0.064
How the predictions were used
PP3 REVEL score is 0.577, which is below the VCEP-recommended threshold of ≥0.70 for PP3. SpliceAI delta score is 0.00, indicating no predicted splice impact. BayesDel score is −0.0637 (benign range). In silico meta-predictors do not support a pathogenic interpretation. Details ▾Hide ▴
Evidence considered
- REVEL=0.577 (<0.70 PP3 threshold)
- SpliceAI max delta=0.00 (no splice impact)
- BayesDel=−0.0637 (benign direction)
Sources
BP4 REVEL score is 0.577, which exceeds the VCEP BP4 threshold of ≤0.40. BayesDel score is −0.0637, indicating a slight benign prediction, but the VCEP-recommended REVEL meta-predictor does not support a benign interpretation. SpliceAI delta score is 0.00, consistent with no splice impact. Details ▾Hide ▴
Evidence considered
- REVEL=0.577 (>0.40 BP4 threshold)
- SpliceAI max delta=0.00 (no splice impact)
- BayesDel=−0.0637 (benign but not the recommended meta-predictor)
Sources
BP7 N/ABP7 applies to synonymous variants and intronic variants outside the splice consensus sequence. This variant is a missense substitution (c.4909G>A, p.Ala1637Thr) and does not qualify for BP7. SpliceAI predicts no splice impact (delta=0.00), but BP7 is structurally not applicable to missense variants. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous or intronic
- SpliceAI delta=0.00 but BP7 not applicable to missense
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.577. BayesDel score = -0.0637112.
10 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
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PMID 23782526 ↗Somatic MYH7, MYBPC3, TPM1, TNNT2 and TNNI3 mutations in sporadic hypertrophic cardiomyopathy.Núñez L et al. · 2013NM_000257.4:c.4909G>A (p.Ala1637Thr) identified in 1 of 104 unrelated HCM patients in a Spanish cohort screened for somatic MYH7, MYBPC3, TPM1, TNNT2, and TNNI3 mutations. All five in silico tools (SIFT, Pmut, PolyPhen, SNAP, PhDSNP) predicted the variant as neutral. No somatic mosaicism was detected; the variant was confirmed germline. No functional or segregation studies were performed for this variant.Names this variant
Quoted passage
Moreover, 2 of these were variants, R845K and A1637T, predicted to be neutral by all 5 methods.
Table 3 (Mutations Found in MYH7 Gene); Results, Novel Mutations in MYH7 paragraph; Discussion, lines 763-767
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PMID 24033266 ↗A systematic approach to assessing the clinical significance of genetic variants.Describes a variant assessment tool (VAT) for systematic evaluation of clinical genetic variants using ACMG guidelines. NM_000257.4:c.4909G>A (p.Ala1637Thr) was not identified in this paper.Does not name this variant
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards S et al. · 2015ACMG/AMP standards and guidelines for interpretation of sequence variants. Provides the generic classification framework. NM_000257.4:c.4909G>A (p.Ala1637Thr) was not discussed in this paper.Does not name this variant
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PMID 29300372 ↗Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel.Kelly MA et al. · 2018Kelly et al. 2018 describes adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies. This is the ClinGen Cardiomyopathy Expert Panel VCEP framework paper that establishes the PM2, PM1, BS1, and other MYH7-specific thresholds. NM_000257.4:c.4909G>A (p.Ala1637Thr) was not individually discussed.Does not name this variant
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PMID 20301725 ↗Nonsyndromic Hypertrophic Cardiomyopathy Overview.Adam MP et al. · 1993GeneReviews overview of nonsyndromic hypertrophic cardiomyopathy. Discusses MYH7 as a major HCM gene with autosomal dominant inheritance. NM_000257.4:c.4909G>A (p.Ala1637Thr) was not identified in the abstract.Does not name this variant
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PMID 20624503 ↗Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy.Millat G et al. · 2010Millat et al. 2010 reports prevalence and spectrum of mutations in 192 unrelated HCM patients. Screened MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL2, MYL3, and ACTC1. NM_000257.4:c.4909G>A (p.Ala1637Thr) was not identified in the abstract.Does not name this variant
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PMID 21267010 ↗Clinical utility gene card for: hypertrophic cardiomyopathy (type 1-14).Clinical utility gene card for hypertrophic cardiomyopathy (types 1-14). NM_000257.4:c.4909G>A (p.Ala1637Thr) was not identified in the abstract.Does not name this variant
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PMID 22958901 ↗Burden of rare sarcomere gene variants in the Framingham and Jackson Heart Study cohorts.Bick AG et al. · 2012Bick et al. 2012 examines burden of rare sarcomere gene variants in the Framingham and Jackson Heart Study cohorts. NM_000257.4:c.4909G>A (p.Ala1637Thr) was not identified in the abstract.Does not name this variant
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PMID 14607462 ↗American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines.ACC/ESC clinical expert consensus document on hypertrophic cardiomyopathy. NM_000257.4:c.4909G>A (p.Ala1637Thr) was not identified.Does not name this variant
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PMID 23403236 ↗Roadmap to determine the point mutations involved in cardiomyopathy disorder: a Bayesian approach.Kumar A et al. · 2013Kumar et al. 2013 describes a Bayesian approach to determine point mutations involved in cardiomyopathy. NM_000257.4:c.4909G>A (p.Ala1637Thr) was not identified.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
128 / 1,614,080 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
7 Likely benign · 3 Uncertain significance · 1 Benign · 1 Uncertain Significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/135637574
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/43044/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/14-23885257-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr14-23416048-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/14-23416048-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000257.4%3Ac.4909…
- OncoKB ↗www.oncokb.org/gene/MYH7/A1637T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=MYH7+c.4909G%3EA
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 7.93021e-05; MAF= 0.00793%, 128/1614080 alleles, homozygotes = 1) and has highest observed frequency in the African/African American population (AF= 0.000987562; MAF= 0.09876%, 74/74932 alleles, homozygotes = 1); grpmax FAF= 0.00080614.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 8.83986e-05; MAF= 0.00884%, 25/282810 alleles, homozygotes = 1) and has highest observed frequency in the African/African American population (AF= 0.00088141; MAF= 0.08814%, 22/24960 alleles, homozygotes = 1); grpmax FAF= 0.00062247.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.00016291951775822744, 3/18414 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Likely benign (7 clinical laboratories) and as Uncertain significance (3 clinical laboratories) and as Benign (1 clinical laboratory) and as Uncertain Significance (1 clinical laboratory) and as Likely Benign by ClinGen Cardiomyopathy Variant Curation Expert Panel (expert panel). (ClinVarID = 43044)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.577. BayesDel score = -0.0637112.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.