NM_000432.3(MYL2):c.260G>C (p.Gly87Ala) AND Primary familial hypertrophic cardiomyopathy

Clinical significance:Likely pathogenic (Last evaluated: Jan 26, 2012)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000036387.2

Allele description [Variation Report for NM_000432.3(MYL2):c.260G>C (p.Gly87Ala)]

NM_000432.3(MYL2):c.260G>C (p.Gly87Ala)

Gene:
MYL2:myosin light chain 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.11
Genomic location:
Preferred name:
NM_000432.3(MYL2):c.260G>C (p.Gly87Ala)
HGVS:
  • NC_000012.12:g.110914200C>G
  • NG_007554.1:g.11378G>C
  • NM_000432.3:c.260G>C
  • NP_000423.2:p.Gly87Ala
  • LRG_393t1:c.260G>C
  • LRG_393:g.11378G>C
  • LRG_393p1:p.Gly87Ala
  • NC_000012.11:g.111352004C>G
  • c.260G>C
Protein change:
G87A
Links:
dbSNP: 397516399
NCBI 1000 Genomes Browser:
rs397516399
Molecular consequence:
  • NM_000432.3:c.260G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Primary familial hypertrophic cardiomyopathy (HCM)
Synonyms:
Hypertrophic cardiomyopathy
Identifiers:
MedGen: C0949658; OMIM: PS192600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000060042Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Jan 26, 2012)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided62not providednot providednot providedclinical testing

Citations

PubMed

Dobzhansky-Muller incompatibilities in protein evolution.

Kondrashov AS, Sunyaev S, Kondrashov FA.

Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14878-83.

PubMed [citation]
PMID:
12403824
PMCID:
PMC137512

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000060042.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided6not providednot providedclinical testing PubMed (2)

Description

The Gly87Ala variant has not been reported in the literature, but has been identified by our laboratory where it segregated with disease in 3 individuals with HCM. Glycine (Gly) at position 87 is highly conserved across evolutionarily distant species, increasing the likelihood that the change is pathogenic. In addition, this variant was predicted to be pathogenic using a computational tool, which was validated by our laboratory using a set of cardiomyopathy variants with well-established clinical significance. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided6not provided2not provided

Last Updated: Dec 6, 2016